Objective: To explore the interocular differences in both the increase of corneal higher-order aberrations (HOAs) and axial length elongation, and the correlation between them after orthokeratology lens (OK lens) wear in children with myopic anisometropia. Methods: It was a prospective cohort study. From 2018 to 2019, 31 children with myopic anisometropia who were fitted with OK lenses initially in the Department of Ophthalmology of Peking University Third Hospital were enrolled, including 15 males (30 eyes) and 16 females (32 eyes). The age was (10.7±1.4) years. Before (baseline) and 12 months after wearing OK lenses, corneal aberrations, corneal relative refractive power (corneal RRP, the difference between peripheral corneal refraction and central corneal refraction) and axial length were measured using the Sirius combining a corneal topographer and a tomographer and an IOL-Master intraocular lens biometer in two eyes. Interocular differences in corneal aberrations, corneal RRP and axial length were analyzed by the paired t test and Wilcoxon rank sum test. The Pearson and Spearman correlation analyses were used to explore the correlation between the increase in corneal HOAs, corneal RRP and axial length elongation. Results: At 12 months after wearing OK lenses, 6 children were lost for follow-up, and the data of the remaining 25 children (50 eyes) were evaluated. With 3.0- and 6.0-mm measuring zones of the total cornea and the anterior surface, the increases in total corneal HOAs, coma, spherical aberration of higher myopic eyes were significantly more than fellow lower myopic eyes (all P<0.05). The corneal RRP with 2.0-mm and 2.5-mm radius in the upper cornea and 2.5-mm radius in the inferior cornea of higher myopic eyes were more than fellow lower myopic eyes (t=-2.06, -2.07, -2.42; P=0.05, 0.049, 0.023), but there was no significant interocular difference in corneal RRP in the horizontal meridian direction of the cornea (both the nasal and temporal sides of the cornea) (both P>0.05). The axial length elongation in higher myopic eyes was 0.14 (0.08, 0.20) mm, which was significantly less than that in the contralateral eyes [0.18 (0.14, 0.35) mm] (Z =-3.21, P= 0.001). The interocular difference in axial length decreased from 0.40 (0.34, 0.54) mm at baseline to 0.33 (0.24, 0.54) mm (Z =-3.21, P = 0.001). The increases in HOAs, coma and spherical aberration of the anterior corneal surface with 3.0-mm measuring zone and the increase in coma of the anterior corneal surface with 6.0-mm measuring zone were all negatively correlated with axial length elongation (r=-0.493, -0.606, -0.500, -0.307; P<0.05). But the corneal RRP had no significant correlation with axial length elongation (r=-0.092, -0.104, -0.230, -0.061; P>0.05). Conclusion: After 12 months of OK lens wear, interocular difference in axial length reduced significantly in children with myopic anisometropia, which was related to the larger increase in corneal HOAs of higher myopic eyes than fellow lower myopic eyes, especially coma.